Effective long-term treatment of eating disorders is a significant challenge not only for the affected individual, but also for the health care provider. Even with prolonged clinical treatment aimed at normalizing feeding patterns and attitudes towards food, the remission rates for eating disorders are still less than 50% (Keel et al., 2002
; Keel et al., 1999
). This necessitates developing better research-based treatment options designed at normalizing eating patterns and mitigating factors involved in sustaining binge eating behaviors. A combination of human and animal studies has implicated dopamine mechanisms in binge eating. In both BED and BN, the frequency of polymorphisms of the DAT1
and associated polymorphisms of D2 receptor suggest that dopamine alterations are trait-related
to binge pathology. The data from DIBE animal models suggest that palatable food access under restricted conditions may prevent food–related dopamine release from habituation and in turn, a sustained activity of the accumbens dopamine system may be involved in the state-dependent
mechanisms of binge eating.
Restrictive eating patterns are not commonly reported in individuals with BED (Greeno et al., 1999
). Thus, the dopaminergic alterations reported under calorie restricted conditions seem to be less relevant to BED pathology. However, BED patients may express restricted eating within days rather than across days. Comparing obese BED with non-BED obese, it has been reported that the BED patients under-eat during the mornings and overeat during the evening hours (Raymond et al., 2003
). In addition, while categories of food choices were not reported in the study, BED subjects on “binge days” had a shift in their macronutrient profile to favor high calorie foods. A pattern of eating whereby foods that are more palatable are underconsumed could result in a perceived reward deprivation and a compensatory overeating during binge days. A similar concept of “hedonic deprivation” has been suggested by Lowe and Levine (Lowe and Levine 2005
). Recent work by the Hajnal laboratory suggests that if a food has more complexity and is highly
palatable the accumbens dopamine signaling does not habituate with repeated exposure even when fed ad libitum (Hajnal et al., 2008
). This observation suggests that periods of “hedonic deprivation” associated with more or less access to highly palatable food may be sufficient to cause dopamine alterations to promote bingeing.
Although the concept of reward sensitization and dependence in DIBE models has been reviewed in greater details elsewhere (Avena 2007
; Avena et al., 2006a
; Avena et al., 2008a
), we have to emphasize the ability of highly palatable foods to increase accumbens dopamine signaling each time it is presented. Such an effect is similar to the self-administration of psychostimulants (i.e., cocaine and amphetamine) in rodents, which do not show blunting in accumbens dopamine signaling upon repeated exposure (Torregrossa and Kalivas 2008
). Thus, the binge eating behavior in BED could be driven by food palatability and altered daily eating patterns. All of these effects then could be exacerbated in a select population with polymorphisms in dopamine-related genes further increasing the susceptibility to developing BED.
The convergence of neural adaptive changes in general, and dopamine in particular, on the compulsive behaviors of binge eating and drug use would suggest an association between drug use and the clinical diagnosis of an eating disorder. This concept was examined in a recent meta-analysis of human data (Calero-Elvira et al., 2009
). This study comprised a total of 42,236 subjects from 16 research articles comparing drug use in individuals meeting criteria for AN-R, BED, and BN between those without an eating disorder. There were three relevant findings from this study. First, for drug use in a clustering of all eating disorders there was a small, but significant, standardized positive effect size. Second, in parsing the classes of illicit drugs there was a positive effect for opiates-cannabis, and not psychostimulants. Third, a higher prevalence for drug use was found in BN, lower in BED and least in AN-R. Considering the data presented in this review, the relationship between drug use and BN/BED in the meta-analysis is not surprising. The finding that individuals with eating disorders use more opiate-cannabis drugs over psychostimulants does require further investigation.
The recent finding from the Hoebel laboratory that accumbens dopamine under restricted-fed conditions is enhanced in underweight rats seems to be more appropriate to AN-BP than to BN symptomatology. Even though bulimics tend to fall into the normal range of BMI, they still may be underweight from their individual pre-morbid body weight. Weight suppression is defined as the highest lifetime past weight minus current weight and has been suggested to be a predictor of treatment outcome in BN (Carter et al., 2008
). Indeed, bulimic inpatients with the highest degree of weight suppression had the worst treatment outcome, an effect that was not associated with dietary restraint scores or other psychological assessments (Butryn et al., 2006
). In addition, weight suppression and desire to lose weight has been directly related to binge frequency (Lowe et al., 2007
). This suggests the degree of weight suppression could be another influential behavior in BN that might affect dopamine, an assertion that needs to be verified by prospective neuroimaging studies in bulimic subjects with varying degrees of weight suppression.
One of the defining features of binge eating is the sense of the loss of control of eating. The subjective feeling and the intensity of the loss of control have been regarded by some to be the defining criteria of binge eating, rather than the objective size of the binge (i.e., objective vs., subjective binge, reviewed in Wolfe et al, 2009
). Nonetheless, loss of control is more associated with the helplessness and despair of the eating disorder as reported by patients (Wolfe et al, 2009
). While the neural basis of loss of control was not directly addressed in this review and considering that loss of control is an aspect of drug use, dopamine mechanisms are likely to be involved (at least indirectly) in the loss of control associated with bingeing pathology. Not surprisingly, one effective strategy used in the cognitive behavior therapy of eating disorder is to normalize eating patterns (APA 2000
). Based on the reviewed studies, we believe that such cognitive control is likely to promote a normalization of dopaminergic functions including responsiveness to food-related cues and stimuli.